How Marijuana Causes Memory Loss

Rsearchers have long suggested marijuana can cause memory loss. Now, a new study provides insight on this association, revealing how cannabinoids in the drug activate receptors in the mitochondria of the brain’s memory center to cause amnesia.

Study leader Dr. Giovanni Marsicano, of the University of Bordeaux in France, and team believe their findings – published in the journal Nature – may lead to the development of new therapeutics that target cannabinoid receptors, without the side effect of memory loss.

Cannabinoids are chemicals present in marijuana, as well as synthetic forms of the drug.

According to the National Institute on Drug Abuse (NIDA), there are more than 100 cannabinoids in marijuana, including the main psychoactive compound delta-9-tetrahydrocannabinol (THC).

These cannabinoids are similar in structure to cannabinoids that occur in the body naturally, such as anandamide. Naturally occurring cannabinoids function as neurotransmitters; they send signals between nerve cells, or neurons, affecting various brain regions, including those responsible for emotion, movement, coordination, sensory perception, and memory and thinking.

The model of the CB1 receptor demonstrates how molecules such as THC bind to and activate it.Image credit: Yekaterina Kadyshevskaya, Stevens Laboratory, USC

Because THC and other cannabinoids present in marijuana and synthetic forms are similar to naturally occurring cannabinoids, they are able to bind to cannabinoid receptors situated on neurons and activate certain brain regions.

As a result, cannabinoids can alter normal brain functioning, causing a number of negative mental and physical effects. One such effect may be memory loss; researchers have shown that THC can affect the function of the hippocampus – the brain region responsible for forming memories.

In the new study, Dr. Marsicano and team further explored the relationship between cannabinoids and memory loss.

CB1 cannabinoid receptors in mitochondria regulate memory processes

In recent years, researchers discovered that one cannabinoid receptor called CB1 is located in the mitochondria of nerve cells. Mitochondria are referred to as the “powerhouses” of cells, as they convert the sugar, fat, and proteins we get from food into energy that cells need to function.

For their study, Dr. Marsicano and colleagues used a variety of innovative methods to find that there are CB1 receptors within the mitochondria of hippocampal neurons, and cannabinoids activate these to cause memory loss.

On further investigation, the researchers found that the memory loss triggered by cannabinoids is down to direct activation of CB1 receptors in the mitochondria, which alters mitochondrial activity. CB1 activation blocks the cannabinoid signaling cascade within mitochondria, and it also reduces cellular respiration – a process that enables the conversion of nutrients into energy.

In simple terms, the study shows that CB1 cannabinoid receptors in mitochondria control memory processes by adjusting the energy metabolism of mitochondria.

Confirming their findings, the team discovered that genetically eliminating the CB1 receptor from mitochondria in the hippocampus prevents memory loss. It also reduces the movement of mitochondria and the inhibition of neuronal signaling caused by cannabinoids.

‘Selective intervention’ on CB1 receptors may lead to new therapeutics

Cannabinoids have shown potential benefits for a number of health conditions, including pain, nausea and vomiting, and neurological disorders. However, the researchers note that the use of therapeutic cannabinoids has been hampered by the side effects they present, such as memory loss.

Dr. Marsicano and team believe their findings could fuel the development of new, safer therapies that target cannabinoid receptors.

“[…] a selective intervention on specific CB1 cannabinoid receptors located in the brain in certain specific neurone compartments could be of interest with a view to developing new therapeutic tools based on the most effective and safest cannabinoids in the treatment of certain brain diseases.”

Study co-author Dr. Pedro Grandes, the University of the Basque Country, Spain